Parkinson's Disease in Women and Men: What's the Difference?

Abstract

Increasing evidence points to biological sex as an important factor in the development and phenotypical expression of Parkinson's disease (PD). Risk of developing PD is twice as high in men than women, but women have a higher mortality rate and faster progression of the disease. Moreover, motor and nonmotor symptoms, response to treatments and disease risk factors differ between women and men. Altogether, sex-related differences in PD support the idea that disease development might involve distinct pathogenic mechanisms (or the same mechanism but in a different way) in male and female patients. This review summarizes the most recent knowledge concerning differences between women and men in PD clinical features, risk factors, response to treatments and mechanisms underlying the disease pathophysiology. Unraveling how the pathology differently affect the two sexes might allow the development of tailored interventions and the design of innovative programs that meet the distinct needs of men and women, improving patient care.

Keywords: Parkinson’s disease; dopaminergic neurons; estrogens; gender; neuroinflammation; oxidative stress; risk factors; sex; signs and symptoms.

Fig.1

Differences in PD symptomatology and risk factors between women and men. PD patients show a different clinical phenotype according to the gender. Moreover, distinct factors seem to contribute to PD risk in women and men. GLA, galactosidase alpha.

Fig.2

Impact of biological sex on PD pathophysiology. The figure summarizes the main sex-related differences in the key players of PD pathogenesis, focusing attention on the vulnerability of dopaminergic system (upper part), neuroinflammatory cells (central part) and oxidative stress (lower part). IP10, interferon-inducible protein 10.